Despite myriad challenges, clinicians see room for progress.
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Edited by Robert Langer, Massachusetts Institute of Technology, Cambridge, MA, and approved December 9, 2020 (received for review November 17, 2020)
Significance
The retention and accumulation of biotherapeutic agents within the circulatory system are difficult due to the high velocity of the blood flow, which limits drug leakage and drug concentration in the targeted region. Herein, we propose a tornado-inspired acoustic vortex tweezers to noninvasively collect microbubbles for improved local concentration of up to 1.7-fold in vitro and in vivo. This technique enables systemic drug administration with extremely low doses.
Abstract
Spatially concentrating and manipulating biotherapeutic agents within the circulatory system is a longstanding challenge in medical applications due to the high velocity of blood flow, which greatly limits drug leakage and retention of the drug in the targeted region. To circumvent the disadvantages of current methods for systemic drug delivery, we propose tornado-inspired acoustic vortex tweezer (AVT) that generates net forces for noninvasive intravascular trapping of lipid-shelled gaseous microbubbles (MBs). MBs are used in a diverse range of medical applications, including as ultrasound contrast agents, for permeabilizing vessels, and as drug/gene carriers. We demonstrate that AVT can be used to successfully trap MBs and increase their local concentration in both static and flow conditions. Furthermore, MBs signals within mouse capillaries could be locally improved 1.7-fold and the location of trapped MBs could still be manipulated during the initiation of AVT. The proposed AVT technique is a compact, easy-to-use, and biocompatible method that enables systemic drug administration with extremely low doses.
Footnotes
- ↵1To whom correspondence may be addressed. Email: ckyeh{at}mx.nthu.edu.tw.
Author contributions: W.-C.L., C.-H.F., Y.-J.H., C.-W.L., and C.-K.Y. designed research; W.-C.L., C.-H.F., Y.-J.H., and C.-W.L. performed research; W.-C.L., C.-H.F., and Y.-J.H. analyzed data; and W.-C.L., C.-H.F., Y.-J.H., and C.-K.Y. wrote the paper.
The authors declare no competing interest.
This article is a PNAS Direct Submission.
This article contains supporting information online at https://www.pnas.org/lookup/suppl/doi:10.1073/pnas.2023188118/-/DCSupplemental.
Data Availability.
All associated protocols and materials are provided in Materials and Methods and SI Appendix. All relevant data has been uploaded at https://zenodo.org/record/4387943#.X-MEidgzYkl.
Published under the PNAS license.
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Tornado-inspired acoustic vortex tweezer for trapping and manipulating microbubbles
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Article Classifications
- Physical Sciences
- Applied Physical Sciences
- Biological Sciences
- Medical Sciences
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